Immunopathology of the lens. I. Humoral and cellular immune responses to heterologous lens antigens and their roles in ocular inflammation.

Abstract

SUMMARY In experimental rabbits heterologous soluble lens proteins consisting of a-, 3-, and y-crystallins were found to be antigenic; they stimulated a marked antibody response compared to a rather weak T-cell response. The serum antibodies to ac-crystallins appeared first, to be followed by antibodies to 13-and y-crystallins in that order. The rabbits did not respond to heterologous y-crystallins unless these were injected with Freund's adjuvant containing mycobacteria. Incomplete Freund's adjuvant (i.e., without mycobacteria) was found to be an inferior immunoaccelerator so far as lens antigens are concerned. The response to lenticular antigens in both magnitude and duration varied in different rabbits, which suggested to us the important role played by a central control mechanism involving the immune response (Ir) genes.Some of the antibodies in potent lens antisera cross-reacted with mitochondria, endoplasmic reticulum (i.e., microsomes), contractile organelles, and cell nuclei. This explains for the first time at least in part the reasons for the widely observed phenomenon of the reactivity of lens antisera with ocular and extraocular structures. Antibodies to soluble lens proteins as detected by immunofluorescence and immunoperoxidase techniques were shown to be of the IgG class. Systemic heterologous immunisation followed by discission of the lens does not lead to the typical changes of phakoallergic endophthalmitis in the rabbit.

Experimental Lens-Induced Granulomatous Endophthalmitis in Common Laboratory Animals

“…Although care was taken to thoroughly disrupt the lens capsule, rabbits which developed significant complement-fixing antilens antibody titers showed no increase in inflam mation compared to normal controls. A similar observation has been previously reported by Misra et al [11] and Rahi et al [13].…”

“…One report discribes a dissociation between cell-mediated and anti body production in rabbits but the studies employed large sensitizing doses of antigen which would favor such an apparent immune deviation [2], This report, however, does not attempt to clarify the basis for the contradictory observations of prior work [11,13].…”

Antioxidant Modulation of Phacoanaphylactic Endophthalmitis

“…Rahi's [11] studies in rabbits [15] and obser vations on strain differences in immunoresponsiveness to lens proteins are two exam ples of discrepancies between serologic re sponses and tissue inflammation in phacoanaphylactic endophthalmitis [7]. Immunoreactant levels measure a polyclonal response so that the levels of the phlogogenic components may not be accu rately reflected in determinations of total immune complexes or complement fixing antibodies.…”

Antilens antibodies in cataract and inflammatory eye disease: an evaluation of a new technique

“…Therefore, if lens proteins escape into the circulfition they may cause the induction of an autoimmune reaction [1,2]. Indeed, it has been demonstrated in animals that immunisation with either homologous [3], or heterologous [4] lens crystallins leads to antibody production against homologous antigenic determinants. However, it also thought that a degree of 'low zone' tolerance [5] normally exists to one's own lens antigens e.g.…”